Evaluation of the Cytotoxic Effect of Cobalt Oxide Nanoparticles Functionalized by Glucose and Conjugated with Lapatinib (Co₃O₄@Glu-Lapatinib) on a Lung Cancer Cell Line and Evaluation of the Expression of CASP8, mTOR1, and MAPK1 Genes

Lung cancer is one of the most acute types of cancer that cannot be easily treated with current treatments. In this study, Co₃O₄ nanoparticles were synthesized and functionalized by glucose and conjugated with Lapatinib. Physicochemical properties of the Co₃O₄@Glu- Lapatinib nanoparticles were characterized by FT-IR, XRD, EDS-mapping, SEM, TEM, DLS, and zeta potential analysis. The viability of the lung cancer and lung fibroblast cells treated with different concentrations of Co₃O₄@Glu-Lapatinib, Lapatinib and Co₃O₄ were investigated by MTT assay. The effect of the nanoparticles on cell cycle and cell apoptosis was determined by flow cytometry and Hoechst staining assays. The relative expression of the CASP8, mTOR1, and MAPK1 genes was also quantified using a real-time PCR assay. The synthesized nanoparticles were spherical, with a size of 29–64 nm, zeta potential of 36.8 mV, DLS size of 323 nm, and without elemental impurities. Co₃O₄@Glu-Lapatinib nanoparticles showed concentration-dependent toxicity on the studied cell lines and were significantly more toxic for the breast cancer cells than breast fibroblast cells with IC₅₀ values of 89 and 178 µg/ml, respectively. Treating cancer cells with Co₃O₄@Glu-Lapatinib nanoparticles increased cell cycle arrest at the sub-G1 and G0/G1 phases and increased the percentage of apoptotic cells from 0.83 to 88.75%. Furthermore, treating cancer cells with the nanoparticles led to overexpression of the CASP8 and MAPK1 genes by 4.48 and 3.4 folds, respectively, while down-regulated the mTOR1 gene by 0.62 folds. Co₃O₄@Glu-Lapatinib nanoparticles can exert antiproliferative effects on lung cancer cells through the inhibition of growth signaling factors and activation of apoptogenic mechanisms.